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The primary objective of this study was to evaluate the frequency of moderate to severe daily hot flashes 4 weeks after a single dose of erenumab (AMG 334) in women with hot flashes associated with menopause.
This study will test the hypothesis that the vasodilation associated with capsaicin-induced dermal blood flow (DBF) provides a good model for the vasodilation associated with hot flashes; therefore erenumab doses that cause DBF inhibition will be safe and well tolerated, and will be effective in the reduction of the frequency and/or severity of HFs.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Participants received a single dose of placebo administered by subcutaneous injection. |
|
| Erenumab | Experimental | Participants received a single dose of 70 mg erenumab administered by subcutaneous injection. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Erenumab | Biological | Administered via subcutaneous injection. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Ratio of Week 4 to Baseline Average Number of Daily Moderate to Severe Hot Flashes | The severity of hot flashes was assessed by participants based on the following categories:
Baseline (BL) number of hot flashes is the average number of moderate or severe hot flashes per 24 hours from day -7 to day 1 predose based on geometric mean, and the week 4 number of hot flashes is the average number of moderate or severe hot flashes per 24 hours from day 21 to day 27 based on geometric mean. The ratio of week 4 to BL was used to assess change from BL to week 4 via a log transformation (log[week4/BL] = log[week4] - log[BL]), which was estimated using a repeated measures analysis. The ratio was obtained via an exponential back-transformation. | Baseline (days -7 to day 1 predose) and week 4 (days 21 to 27) |
| Measure | Description | Time Frame |
|---|---|---|
| Ratio of Week 4 to Baseline Daily Hot Flash Severity Score | The daily severity score was calculated according to the following: (Number of mild hot flashes * 1) + (number of moderate hot flashes * 2) + (number of severe hot flashes * 3). The baseline daily hot flash severity score is the geometric mean daily hot flash severity score from day -7 to day 1 predose, and the week 4 daily hot flash severity score is the geometric mean daily hot flash severity score from day 21 to day 27. The ratio of week 4 to baseline (week 4 / baseline) was used to assess change from baseline to week 4 via a log transformation (log[week4/BL] = log[week4] - log[baseline]), which was estimated using a repeated measures analysis. The ratio was obtained via an exponential back-transformation. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| MD | Amgen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | San Diego | California | 92108 | United States | ||
| Research Site |
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| Label | URL |
|---|---|
| AmgenTrials clinical trials website | View source |
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Participants meeting the eligibility criteria were randomized in a 1:1 ratio to erenumab or placebo. Participants were stratified based on the average number of hot flashes per 24 hours during the screening period (≤ 11.5 or > 11.5).
This study was conducted at 6 centers in the United States from 13 May 2013 to 11 March 2014.
Screening included completion of a 7-day diary to record hot flashes.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Participants received a single dose of placebo administered by subcutaneous injection. |
| FG001 | Erenumab | Participants received a single dose of 70 mg erenumab administered by subcutaneous injection. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Participants who received study treatment.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Participants received a single dose of placebo administered by subcutaneous injection. |
| BG001 | Erenumab | Participants received a single dose of 70 mg erenumab administered by subcutaneous injection. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Ratio of Week 4 to Baseline Average Number of Daily Moderate to Severe Hot Flashes | The severity of hot flashes was assessed by participants based on the following categories:
Baseline (BL) number of hot flashes is the average number of moderate or severe hot flashes per 24 hours from day -7 to day 1 predose based on geometric mean, and the week 4 number of hot flashes is the average number of moderate or severe hot flashes per 24 hours from day 21 to day 27 based on geometric mean. The ratio of week 4 to BL was used to assess change from BL to week 4 via a log transformation (log[week4/BL] = log[week4] - log[BL]), which was estimated using a repeated measures analysis. The ratio was obtained via an exponential back-transformation. | All participants for whom at least 1 postdose hot flash response measure was recorded. | Posted | Number | 95% Confidence Interval | ratio | Baseline (days -7 to day 1 predose) and week 4 (days 21 to 27) |
16 Weeks
Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants received a single dose of placebo administered by subcutaneous injection. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Upper respiratory tract infection | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Amgen Inc. | 866-572-6436 | medinfo@amgen.com |
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| ID | Term |
|---|---|
| D019584 | Hot Flashes |
| ID | Term |
|---|---|
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C000605816 | erenumab |
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| Placebo | Drug | Administered via subcutaneous injection |
|
| Baseline (days -7 to day 1 predose) and week 4 (days 21 to 27) |
| Number of Participants With Treatment-emergent Adverse Events | A treatment-emergent adverse event is any adverse event that began or worsened after the initial dose of study drug and before the end of study. A serious adverse event is an adverse event that met at least 1 of the following serious criteria:
| 16 weeks |
| Maximum Observed Concentration (Cmax) of Erenumab After a Single Dose | Blood samples were analyzed using an enzyme-linked immunosorbent assay (ELISA) following a validated analytical procedure. | Predose and 4 hours, 2, 3, 4, 8, 12, 15, 22, 29, 43, 50, 57, 64, 78, 85, and 113 days post-dose |
| Time to Maximum Observed Concentration (Tmax) of Erunumab After a Single Dose | Predose and 4 hours, 2, 3, 4, 8, 12, 15, 22, 29, 43, 50, 57, 64, 78, 85, and 113 days post-dose |
| Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) for Erenumab | Predose and 4 hours, 2, 3, 4, 8, 12, 15, 22, 29, 43, 50, 57, 64, 78, 85, and 113 days post-dose |
| Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for Erenumab | Predose and 4 hours, 2, 3, 4, 8, 12, 15, 22, 29, 43, 50, 57, 64, 78, 85, and 113 days post-dose |
| Terminal Half-life (T1/2) of Erenumab | Predose and 4 hours, 2, 3, 4, 8, 12, 15, 22, 29, 43, 50, 57, 64, 78, 85, and 113 days post-dose |
| Number of Participants With Treatment-emergent Suicidal Ideation | The Columbia Suicide Severity Rating Scale (C-SSRS) was used to assess suicidal ideation during the study based on the following Yes/No questions:
| 16 weeks |
| Number of Participants Who Developed Anti-erenumab Antibodies After a Single Dose | Two validated assays were used to detect the presence of anti-erenumab antibodies. First, an electrochemiluminescent (ECL) bridging immunoassay was used to detect antibodies capable of binding erenumab. Second, a cell based bioassay was used to test positive binding antibody samples for neutralizing activity against erenumab. A participant was defined as positive for developing anti-erenumab antibodies if they were binding antibody positive postbaseline with a negative or no result at baseline. If a sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the participant was defined as positive for neutralizing antibodies. | 16 weeks |
| Miami |
| Florida |
| 33186 |
| United States |
| Research Site | Winston-Salem | North Carolina | 27103 | United States |
| Eugene Andruczyk | Philadelphia | Pennsylvania | 19114 | United States |
| Research Site | Philadelphia | Pennsylvania | 19114 | United States |
| Research Site | Mt. Pleasant | South Carolina | 29464 | United States |
| Research Site | Seattle | Washington | 98105 | United States |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Number of Hot Flashes at Baseline | Baseline number of hot flashes is the average number of moderate or severe hot flashes per 24 hours from day -7 to day 1 predose. | Count of Participants | Participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Placebo | Participants received a single dose of placebo administered by subcutaneous injection. |
| OG001 | Erenumab | Participants received a single dose of 70 mg erenumab administered by subcutaneous injection. |
|
|
|
| Secondary | Ratio of Week 4 to Baseline Daily Hot Flash Severity Score | The daily severity score was calculated according to the following: (Number of mild hot flashes * 1) + (number of moderate hot flashes * 2) + (number of severe hot flashes * 3). The baseline daily hot flash severity score is the geometric mean daily hot flash severity score from day -7 to day 1 predose, and the week 4 daily hot flash severity score is the geometric mean daily hot flash severity score from day 21 to day 27. The ratio of week 4 to baseline (week 4 / baseline) was used to assess change from baseline to week 4 via a log transformation (log[week4/BL] = log[week4] - log[baseline]), which was estimated using a repeated measures analysis. The ratio was obtained via an exponential back-transformation. | All participants for whom at least 1 postdose hot flash response measure was recorded. | Posted | Number | 95% Confidence Interval | ratio | Baseline (days -7 to day 1 predose) and week 4 (days 21 to 27) |
|
|
|
|
| Secondary | Number of Participants With Treatment-emergent Adverse Events | A treatment-emergent adverse event is any adverse event that began or worsened after the initial dose of study drug and before the end of study. A serious adverse event is an adverse event that met at least 1 of the following serious criteria:
| All participants who received study drug | Posted | Count of Participants | Participants | 16 weeks |
|
|
|
| Secondary | Maximum Observed Concentration (Cmax) of Erenumab After a Single Dose | Blood samples were analyzed using an enzyme-linked immunosorbent assay (ELISA) following a validated analytical procedure. | All participants who received erenumab and for whom at least 1 pharmacokinetic (PK) parameter or endpoint could be adequately estimated. | Posted | Mean | Standard Deviation | μg/mL | Predose and 4 hours, 2, 3, 4, 8, 12, 15, 22, 29, 43, 50, 57, 64, 78, 85, and 113 days post-dose |
|
|
|
| Secondary | Time to Maximum Observed Concentration (Tmax) of Erunumab After a Single Dose | All participants who received erenumab and for whom at least 1 pharmacokinetic (PK) parameter or endpoint could be adequately estimated. | Posted | Median | Full Range | days | Predose and 4 hours, 2, 3, 4, 8, 12, 15, 22, 29, 43, 50, 57, 64, 78, 85, and 113 days post-dose |
|
|
|
| Secondary | Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) for Erenumab | All participants who received erenumab and for whom at least 1 pharmacokinetic (PK) parameter or endpoint could be adequately estimated. | Posted | Mean | Standard Deviation | day*μg/mL | Predose and 4 hours, 2, 3, 4, 8, 12, 15, 22, 29, 43, 50, 57, 64, 78, 85, and 113 days post-dose |
|
|
|
| Secondary | Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for Erenumab | All participants who received erenumab and for whom at least 1 pharmacokinetic (PK) parameter or endpoint could be adequately estimated. AUCinf could not be accurately estimated for 23 participants who are excluded from the analysis. | Posted | Mean | Standard Deviation | day*μg/mL | Predose and 4 hours, 2, 3, 4, 8, 12, 15, 22, 29, 43, 50, 57, 64, 78, 85, and 113 days post-dose |
|
|
|
| Secondary | Terminal Half-life (T1/2) of Erenumab | All participants who received erenumab and for whom at least 1 PK parameter or endpoint could be adequately estimated. T1/2 could not be accurately estimated for 23 participants who are excluded from the analysis. The terminal half-life calculated from this single dose study may not be representative of a clinically relevant half-life of erenumab. | Posted | Mean | Standard Deviation | days | Predose and 4 hours, 2, 3, 4, 8, 12, 15, 22, 29, 43, 50, 57, 64, 78, 85, and 113 days post-dose |
|
|
|
| Secondary | Number of Participants With Treatment-emergent Suicidal Ideation | The Columbia Suicide Severity Rating Scale (C-SSRS) was used to assess suicidal ideation during the study based on the following Yes/No questions:
| All participants who received study drug | Posted | Count of Participants | Participants | 16 weeks |
|
|
|
| Secondary | Number of Participants Who Developed Anti-erenumab Antibodies After a Single Dose | Two validated assays were used to detect the presence of anti-erenumab antibodies. First, an electrochemiluminescent (ECL) bridging immunoassay was used to detect antibodies capable of binding erenumab. Second, a cell based bioassay was used to test positive binding antibody samples for neutralizing activity against erenumab. A participant was defined as positive for developing anti-erenumab antibodies if they were binding antibody positive postbaseline with a negative or no result at baseline. If a sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the participant was defined as positive for neutralizing antibodies. | All participants who received study drug. | Posted | Count of Participants | Participants | 16 weeks |
|
|
|
| 0 |
| 52 |
| 11 |
| 52 |
| EG001 | Erenumab 70 mg | Participants received a single dose of 70 mg erenumab administered by subcutaneous injection. | 0 | 50 | 9 | 50 |
| Urinary tract infection | Infections and infestations | MedDRA 17.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 17.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 17.0 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 17.0 | Systematic Assessment |
|
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
| TEAE leading to discontinuation of study drug |
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| TEAE leading to discontinuation of study |
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| Fatal adverse events |
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| Treatment-related adverse events (TRAEs) |
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| Treatment-related serious adverse events |
|
| TRAE leading to discontinuation of study drug |
|
| TRAE leading to discontinuation of study |
|
| Treatment-related fatal adverse events |
|